RNA editing produces glycine receptor α3P185L, resulting in high agonist potency

The function of supramedullary glycine receptors (GlyRs) is still unclear. Using Wistar rat collicular slices, we demonstrate GlyR-mediated inhibition of spike discharge elicited by low glycine ( 10 mu M). Searching for the molecular basis of this phenomenon, we identified a new GlyR isoform. GlyR alpha 3(P185L), a result of cytidine 554 deamination, confers high glycine sensitivity (EC50 similar to 5 mu M) to neurons and thereby promotes the generation of sustained chloride conductances associated with tonic inhibition. The level of GlyR alpha 3-C554U RNA editing is sensitive to experimentally induced brain lesion, inhibition of cytidine deamination by zebularine and inhibition of mRNA transcription by actinomycin D, but not to blockade of protein synthesis by cycloheximide. Conditional regulation of GlyR alpha 3(P185L) is thus likely to be part of a post-transcriptional adaptive mechanism in neurons with enhanced excitability.